Efficacy of Reduced Dose BCG Treatment in Response to Production Shortages - Expert Commentary

Bacillus Calmette-Guérin (BCG) has long been considered a standard of care in treating intermediate-risk or high-risk non-muscle invasive bladder cancer (NMIBC). For maintenance, recommendations stipulate a 1-year treatment for intermediate-risk patients and up to 3 years for high-risk patients.

However, BCG production has had a severe global shortage over the past ten years. As a result, clinicians have been forced to find alternative treatment methods while others have used lower doses of BCG instead. Lobo et al. treated NMIBC patients with a third of the traditional BCG dose and assessed patient outcomes to determine the real-world effects of this modified treatment regimen.

The retrospective cohort included 563 NMIBC patients, among whom 413 received full dose BCG while 150 received a third dose. Patients in the reduced dose group were more likely to have low-grade or solitary tumors and the absence of concomitant carcinoma in situ. The median number of BCG doses administered to reduced dose and full dose patients was 18 and 21 doses, respectively. The median time from transurethral resection of bladder tumor (TURBT) to starting BCG treatment was the same across all patients. The overall median follow-up period was 54.8 months, with 35.2% of patients exhibiting recurrence. Among these patients, 34% had received the reduced dose, while 35.6% had received the full dose. Disease progression was observed in 5.3% of reduced-dose patients and 8.5% of full-dose patients. Analysis of time to progression revealed no significant difference between the two groups.

Radical cystectomies occurred in 10% of reduced-dose patients and 10.9% of full-dose patients. Approximately 17.8% of the patients in the cohort died. The proportion of bladder cancer-related deaths was 1.3% in patients who received the reduced dose and 4.4% in patients who received the full dose of BCG. The 5-year cancer-specific survival rate was 98.5% in the reduced dose group and 95.7% in the full dose group.

Lobo et al. confirm the feasibility of using a reduced dose of BCG in treating NMIBC patients. Administering a third of the usual BCG dose did not result in inferior outcomes compared to full-dose treatment. This alternative can help increase the available doses for more patients as a single vial was divided among three patients in the reduced dose protocol. However, it should be noted that this technique does not comply with the manufacturer’s recommendations of using BCG within 2 hours after reconstitution. Nevertheless, Lobo et al. previously demonstrated its viability after 8 hours and even 72 hours after reconstitution. These practical issues will need to be analyzed at different institutions that may opt for a reduced dose treatment. Other factors that need to be considered include the variability in the BCG content in different batches. Ongoing research will test the efficacy of alternative BCG strains and identify alternative intravesical therapies.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

References:

  1. Lobo N, Bree KK, Hensley PJ, et al. Reduced-dose bacillus Calmette-Guérin (BCG) in an era of BCG shortage: real-world experience from a tertiary cancer centre. BJU Int. 2022;130(3):323-330. doi:10.1111/bju.15661

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